Microdroplets have a wide variety of applications. Droplets in microfluidic systems can work as “miniaturized reactors” because of their unique features including high-throughput, minimal reagent consumption, ability to be contamination-free, fast response times, and their ability to isolate individual spaces. Therefore, droplet-based microfluidics has emerged as a potential platform for applications such as chemical and biological assays, synthesis, reactions, drug delivery, and diagnostic testing and screening. A commercialized technology based on microdroplets is digital polymerase chain reactions (dPCR), in which a diluted sample is partitioned into reaction chambers to achieve superior sensitivity and quantification based on single molecule assays. In the past two years, several dPCR instruments based on microdroplet/microwell technology have been developed. It is desirable for these instruments to produce a large number of microdroplets that are uniform in size and small in volume. Although production of millions of microdroplets with a unit volume of a few picoliters (pL) has been demonstrated within half an hour (e.g., with a droplet generation rate of ˜5.5 kHz), most of the instruments for producing such microdroplets are expensive and have complex operating schemes.
Conventional methods for producing high volumes of microdroplets generally rely on agitation and sonication methods. However, it is difficult to produce monodispersed (uniform) droplets with such methods because of the spatial heterogeneity of the applied mechanical stress. Another widely adopted industrial method for high-throughput droplet generation is membrane emulsification, in which a dispersed fluid is pressurized and passes through a porous membrane. However, variation of pore diameter in the membrane and mutual interference from adjacent droplets often results in a polydispersed (non-uniform) distribution of generated droplets. Therefore, these two approaches are limited to being used when the droplet quality is not required to be high, such as in food processing or medicine atomization.
Another approach to forming microdroplets is shear-based systems (e.g., T-junction or flow-focusing structures). In these structures, the dispersed phase is squeezed in a main channel, and fractures of the dispersed fluid occur in the continuous phase under the action of shear forces, forming individual microdroplets. Most of the energy in this method is dissipated by the flow of the continuous phase, and a small portion is used to overcome the surface tension of the dispersed phase to generate droplets. It is difficult, if not impossible, to achieve high frequency (e.g., a few kHz) droplet formation from a single unit using this method. In addition, this method makes it difficult to obtain uniform droplet size when many individual droplet forming units are parallelized, because precise pressure and volume control is required for both phases. Therefore, highly uniform droplet generation using this method is difficult, if not impossible, to scale.
Another category of droplet generators is interfacial tension driven systems (e.g., grooved microchannels, edge-based/step emulsification). Only control of the dispersed phase is required for droplet break-up in these systems, which makes parallelization easier. The scalability and compact size of these devices may also provide the potential to further improve droplet generation volume. However, there are still challenges to be addressed in reducing the droplet size, improving the droplet monodispersity (uniformity), minimizing interference between droplet formation units, and stabilizing system dynamics.